Synthesis and Evaluation of New Trivalent Ligands for Hepatocyte Targeting via the Asialoglycoprotein Receptor.

Since the asialoglycoprotein receptor (also known as the "Ashwell-Morell receptor" or ASGPR) was discovered as the first cellular mammalian lectin, numerous drug delivery systems have been developed and several gene delivery systems associated with multivalent ligands for liver disease targeting are undergoing clinical trials. The success of these systems has facilitated the further study of new ligands with comparable or higher affinity and less synthetic complexity. Herein, we designed two novel trivalent ligands based on the esterification of tris(hydroxymethyl) aminomethane (TRIS) followed by the azide-alkyne Huisgen cycloaddition with azido -acetyl-d-galactosamine.

Synthesis of new ,'-Pd(Pt) complexes based on sulfanyl pyrazoles, and investigation of their anticancer activity.

The synthesis of new ,'-mononuclear bi-ligand Pd(ii) and tri-ligand Pt(ii)complexes bearing sulfanyl(phenyl, benzyl, cyclohexyl, 4-hydroxyphenyl)3,5-dimethyl-1-pyrazole ligands has been carried out. The obtained compounds were studied for apoptosis-inducing activity and effect on the cell cycle for Jurkat, K562, and U937 neoplastic cell cultures and conditionally normal human embryonic kidney HEK293 cells. The cells showed the highest sensitivity to platinum and palladium complexes in comparison with ligands and cisplatin.

Methotrexate-loaded metal-organic frameworks on the basis of γ-cyclodextrin: Design, characterization, in vitro and in vivo investigation.

In this work, metal-organic frameworks on the basis of γ-cyclodextrin (γCD-MOF) were proposed as carriers for methotrexate (MTX) which is widely used as chemotherapy agent and immune system suppressant. The synthesized γCD-MOF was loaded with MTX by impregnation and co-crystallization. The obtained composites were characterized using powder X-ray diffraction, N adsorption/desorption, FTIR spectroscopy, solid-state C MAS CP/TOSS NMR and scanning electron microscopy.

Synthesis of C17-[5-methyl-1,3]-oxazoles by -propargylation of triterpenic acids and evaluation of their cytotoxic activity.

A series of unexpected triterpenic C17-[5-methyl-1,3]-oxazoles along with targeted -propargylamides was synthesized by an interaction of acid chlorides with propargylamine hydrochloride. We proposed that the formation of methyl oxazole passes through an alternative pathway by the participation of the terminal alkyne carbon atom and acid chloride intermediate with following intramolecular rearrangements. The synthesized compounds were evaluated for their cytotoxicity at the U.

Development of solvent-free protocols for obtaining highly substituted maleates of hyaluronic acid and other glycosaminoglycans.

Solvent-free protocols using microwave-assisted heating (i) or conventional heating without additives (ii) or adding KCO (iii), or triturating at room temperature in the presence of KCO (iv) were first used to esterify glycosaminoglycans (GAG) with maleic anhydride. High and low molecular weight hyaluronic acid (HMW and LMW HA), dermatan sulfate (Ds), heparin (HEP) and C6-oxidized HA (carboxy-HA) were used as substrates for maleation. Protocols (i)-(iii) were most effective for obtaining maleates with high DS (1.

Effect of structural factors on the physicochemical properties of functionalized polyanilines.

This review discusses the physical and physicochemical properties of polyaniline (PANI) derivatives. The most important methods for the preparation of functionalized polyanilines are presented. The presence of various substituents in its structure changes the polymer characteristics significantly due to steric and electronic effects of the functional groups.

Synthesis and In Vitro Anticancer Activity of 6-Ferrocenylpyrimidin-4(3H)-one Derivatives.

Aim And Objective: Some ferrocenyl derivatives are active in vitro and in vivo against cancer. Generally, ferrocenyl derivatives for cancer research have three key components: a ferrocene moiety, a conjugated linker that lowers the oxidation potential and some derivative (peptide, nucleobase and others) that can interact with biomolecules. Since the pyrimidine fragment can easily pass through the membrane into the cells and become involved in metabolism; it appears to be promising.

The Introduction of Hydrazone, Hydrazide, or Azepane Moieties to the Triterpenoid Core Enhances an Activity Against .

Background: Triterpenoids exhibit a wide spectrum of antimicrobial activity.

Objective: The objective of this study was to synthesize a series of nitrogen derivatives based on lupane, oleanane, and ursane triterpenoids with high antitubercular activity.

Methods: Isonicotinoylhydrazones were prepared via the reaction of 3-oxotriterpenic acids or betulonic aldehyde with isoniazid (INH) in yields of 54-72%.

Experimental and theoretical substantiation of differences of geometric isomers of copper(II) α-amino acid chelates in ATR-FTIR spectra.

Stereo and structural isomerism of the copper(II) chelate complexes define their biological activity. At the same time, the identification of the geometric isomers of such complexes is a nontrivial task of modern coordination chemistry. In the presented work we have studied the trans- and cis-isomers of chelates bis(S-valinato)copper(II), (R,S-valinato)copper(II) and other mixed ligand copper(II) amino acid complexes with the joint use of experimental by ATR-FTIR spectroscopy and DFT simulations.

Antiviral activity of amides and carboxamides of quinolizidine alkaloid (-)-cytisine against human influenza virus A (H1N1) and parainfluenza virus type 3.

Novel derivatives of quinolizidine alkaloid ()-cytisine were synthesised. ADME properties, cytotoxicity against HEK293 cells and activity against viruses of influenza A/California/07/09(H1N1)pdm09 virus (IAV) and human parainfluenza virus type 3 (HPIV3) were evaluated. It was shown, that 9-carboxamides of methylcytisine (with phenyl and allyl urea's fragments) are most active compounds against IAV probably due to predicted peculiarity of their interactions with the 4R7B active site of IAV neuraminidase.

The substituent effects on the [3+2] cycloaddition of nitrile oxides generated by photooxidation of arylazides to acetonitrile.

The DFT approach in M06L/6-311 + G(d,p) approximation was used to study the transformation of unsaturated nitrile oxides (RCNO), which were generated by photooxidation of the corresponding aromatic azide, to oxadiazoles via [3 + 2]cyclization with acetonitrile. It was found that the cycloaddition activation enthalpy was within 60-93 kJ/mol, depending on the structure of the nitrile oxide. A significant mesomeric effect of the substituent and its position in the conjugated molecular system on the activation barrier of the reaction studied was identified.

Synthesis and structure-activity relationships of novel camphecene analogues as anti-influenza agents.

A chemical library was constructed based on the scaffold of camphecene (2-(E)-((1R,4R)-1,7,7-trimethylbicyclo[2.2.1]heptan-2-ylidene-aminoethanol).

Synthesis of Camphecene and Cytisine Conjugates Using Click Chemistry Methodology and Study of Their Antiviral Activity.

A series of camphecene and quinolizidine alkaloid (-)-cytisine conjugates has been obtained for the first time using 'click' chemistry methodology. The cytotoxicity and virus-inhibiting activity of compounds were determined against MDCK cells and influenza virus A/Puerto Rico/8/34 (H1N1), correspondingly, in in vitro tests. Based on the results obtained, values of 50 % cytotoxic dose (CC ), 50 % inhibition dose (IC ) and selectivity index (SI) were determined for each compound.

Glycyrrhizic acid derivatives as Dengue virus inhibitors.

Dengue virus (DENV) is one of the most geographically distributed pathogenic flaviviruses transmitted by mosquitoes Aedes sps. In this study, the structure-antiviral activity relationships of Glycyrrhizic acid (GL) derivatives was evaluated by the inhibitory assays on the cytopathic effect (CPE) and viral infectivity of DENV type 2 (DENV2) in Vero E6 cells. GL (96% purity) had a low cytotoxicity to Vero E6 cells, inhibited DENV2-induced CPE, and reduced the DENV-2 infectivity with the IC50 of 8.

Paeoniflorin benzoates: synthesis and influence on learning and memory of aged rats in the passive avoidance task.

Paeoniflorin per-O-benzoates with the preserved pinane structure and rearranged aglycone , containing C4 = O function, were obtained and their influence on learning and memory of aged rats was studied in the passive avoidance task. It was found that the chemical modification of paeoniflorin affected the cognitive functions of aged rats. The introduction of C4 = O function into the pinane part of benzoate led to the improvement in learning process and preservation of the memory trace in aged rats as compared to the natural glycoside.

Three (-)-cytisine derivatives and 1-hydroxyquinopimaric acid as acetylcholinesterase inhibitors.

acetylcholinesterase (AChE) inhibition was studied using novel derivatives of (-)-cytisine derivatives -allylcytisine-12-carbamide (A-63), cytisine-12-carbamide (A-36), -1-adamantylcytisine-12-thiocarbamide (U-12), and 1-hydroxyquinopimaric acid (U-201). Inhibition of acetylcholinesterase with compound A-63 was described as mixed inhibition. Substances (A-36) and (U-201) acted as competitive inhibitors with Ki equal to 6.

Diastereoselective Synthesis of Triterpenoid 1,2,4-Trioxolanes by Griesbaum Co-ozonolysis.

Diastereoselective synthesis of triterpenoid 1,2,4-trioxolanes by Griesbaum co-ozonolysis was shown for the first time. Ozonolysis of 2-methoxyoximes (--isomers mixture) of allobetulin or methyl oleanoate with CF-ketones resulted in asymmetrical spiro-1,2,4-trioxolanes as mixtures of diastereomers in yields up to 80-85%. The configuration of the spiro-C-2 center of individual ozonides was determined by 2D NMR spectra and X-ray crystallographic analysis.

Luminescent and DFT Study of Keto-Enol Tautomers of 5-Fluorouracil and Its Derivatives in Aqueous Solutions.

Fluorescence (FL) spectra were recorded and identified for the following 5-fluorouracil (FU) tautomers: 5-fluoropyrimidine-2,4(1,3)-dione (), 5-fluoro-2-hydroxypyrimidine-4(3)-one (), and 5-fluoro-4-hydroxypyrimidine-2(1)-one (), as well as the corresponding tautomers and of 1-(tetrahydrofuranyl-2)-5-fluorouracil and 1-methyl-5-fluorouracil, tautomers and of 3-methyl-5-fluorouracil, and the diketo tautomer of 1,3-dimethyl-5-fluorouracil. It was shown that the FL of rare tautomers of FU derivatives occurs by the excitation of uracil homoassociates followed by intramolecular proton transfer (IPT), formation of a pair of rare tautomers, and radiative deactivation of one of them. The FL quantum yields φ were estimated.

Synthesis of new 1,3-thiazol derivatives of maleopimaric acid as anticancer, antibacterial and antifungal agents.

A series of new 1,3-thiazole derivatives of maleopimaric acid , were synthesized and evaluated for anticancer, antibacterial and antifungal activities. Evaluation of cytotoxic activity against human embryonic kidney 293 cells (HEK293), human neuroblastoma cell line (SH-SY5Y), hepatocellular carcinoma cell line (HepG2) and human T-cell lymphoblast-like line (Jurkat), showed that introduction of the aminothiazole fragment at position 6 of the diterpenoid molecule leads to decrease of cell viability. Substance 3 was found to be the most active against all tested cell lines, inhibiting cell viability with IC values in the range of 2-24 μM.

Ribes taxa: A promising source of γ-linolenic acid-rich functional oils.

Fifty Ribes species and R. nigrum-based cultivars from eight Ribes sections were surveyed for γ-linolenic acid (GLA, 18:3, n-6)- and stearidonic acid (SDA, 18:4, n-3)-rich oils. R.

Effects of novel hexahydropyrimidine derivatives as potential ligands of M1 muscarinic acetylcholine receptor on cognitive function, hypoxia-induced lethality, and oxidative stress in rodents.

The neurodegenerative diseases have a complex pathogenetic mechanism comprising oxidative stress and receptor system dysfunction caused by various damaging factors such as, for example, brain hypoxia. The purpose of this study was to elucidate the influence of hexahydropyrimidine derivatives on learning, memory, and orientation and locomotor activities in the passive avoidance (PA) and open field (OF) tests and to evaluate these compounds for their potential antihypoxic and antioxidant action on normobaric hypercapnic hypoxia and toxic hypoxia models. We demonstrated that compounds 1a and 1e administered as a single 100 mg/kg dose (p.

Nucleophilic cyclopropanation of [60]fullerene by the addition-elimination mechanism.

Information on the synthesis of monofunctionalized methanofullerenes C obtained by the addition-elimination mechanism is generalized. The main reagents for cyclopropanation, mechanisms and optimal conditions for the processes, and the prospects for practical application of the products are considered.

Variation of spacer type and topology of phenyl moiety in 2-pyridone core of 4-oxo-3--methylcytisine; effect of synthesized compounds on rat's behavior in conditioned passive avoidance reflex (CPAR) test.

Novel derivatives of 4-oxo-3-methylcytisine with phenyl moiety bonded to starting molecule through various spacers were obtained from the 9-amino, -halo, -formyl and 11-halo precursors by reductive alkylation of amines, generation of amide, as well as thio- and carboxamide functions, cross-coupling reactions, aldehyde condensation and reduction of unsaturated 'C-C' bonds. Ability of synthesized compounds to influence the learning and memory was preliminary assessed in conditioned passive avoidance reflex (CPAR) test in rats. It was shown, that derivatives with phenyl group at 11 carbon atom influence the learning and memory in CPAR test more effectively than other compounds.

Morphological and functional evaluation of the effect of novel pyrimidine derivatives on regeneration of the sciatic nerve in rats.

Two novel pyrimidine derivatives, RG2 and RG6, were studied using a rat's model of peripheral nerve injury. Toe-spreading reflex and skin sensitivity to pinch in the foot were monitored to follow recovery of motor and sensory functions in the treated animals. The remyelation rate in the distal segment of the damaged nerve was also studied using morphological analysis of cross-sections of the nerve stained with methylene blue.

Structural modifications of 2,3-indolobetulinic acid: Design and synthesis of highly potent α-glucosidase inhibitors.

A series of nineteen nitrogen-containing lupane triterpenoids was obtained by modification of C2, C3, C20 and C28 positions of betulonic acid and their α-glucosidase inhibiting activity was investigated. Being a leader compound from our previous study, 2,3-indolo-betulinic acid was used as the main template for different modifications at C-(28)-carboxyl group to obtain cyano-, methylcyanoethoxy-, propargyloxy- and carboxamide derivatives. 20-Oxo- and 29-hydroxy-20-oxo-30-nor-analogues of 2,3-indolo-betulinic acid were synthesized by ozonolysis of betulonic acid followed by Fischer indolization reaction.